RESUMO
Epigenetics, particularly deacetylation, plays a critical role in tumorigenesis as many carcinogens are under tight control by post-translational modification. HDAC6, an important and special histone deacetylase (HDAC) family member, has been indicated to increase carcinogenesis through various functions. Recent studies demonstrated the effects of HDAC6 inhibitors in mitotic arrest, however, detailed mechanisms still remain unknown. Herein, we review and summarize HDAC6-associated proteins that have been implicated in important roles in mitosis. We also discuss the development of medicinal agents targeting HDAC6.
RESUMO
HDAC6, a member of the histone deacetylase family, mainly is a cytosolic protein and regulates cell growth by acting on non-histone substrates, such as α -tubulin, cortactin, heat shock protein HSP90, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), that are closely related to the proliferation, invasion, immune escape and angiogenesis of cancer tissues. The approved drugs targeting the HDACs are all pan-inhibitors and have many side effects due to their lack of selectivity. Therefore, development of selective inhibitors of HDAC6 has attracted much attention in the field of cancer therapy. In this review, we will summarize the relationship between HDAC6 and cancer, and discuss the design strategies of HDAC6 inhibitors for cancer treatment in recent years.
Assuntos
Antineoplásicos , Neoplasias , Humanos , Desacetilase 6 de Histona/metabolismo , Inibidores de Histona Desacetilases/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Histona Desacetilases/metabolismoRESUMO
C-Jun N-terminal kinase (JNK) is a member of mitogen-activated protein kinases (MAPKs) family, with three isoforms, JNK1, JNK2 and JNK3. Alzheimer's disease (AD) is a neurological disorder and the most common type of dementia. Two well-established AD pathologies are the deposition of Aß amyloid plaques and neurofibrillary tangles caused by Tau hyperphosphorylation. JNK3 is involved in forming amyloid Aß and neurofibrillary tangles, suggesting that JNK3 may represent a target to develop treatments for AD. Therefore, this review will discuss the roles of JNK3 in the pathogenesis and treatment of AD, and the latest progress in the development of JNK3 inhibitors.